Prostaglandins and leukotrienes are products of arachidonic acid metabolism via the cyclooxygenase pathway and the lipoxygenase pathway, respectively. Leukotriene B.sub.4 is one of the most potent naturally occurring mediators of inflammation and is a potent chemotactic and chemokinetic agent for leukocytes. Leukotriene B.sub.4 causes in vitro leukocyte accumulation, modulates pain responses and causes changes in vascular permeability. The peptido-lipid conjugates leukotriene C.sub.4, D.sub.4 and E.sub.4 play a lesser role as mediators of inflammation and collectively account for the biological activity known as "slow reacting substance of anaphylaxis". Leukotrienes C.sub.4, D.sub.4 and E.sub.4 are potent smooth muscle contractile agents and are, therefore, believed to be important mediators of asthma and other hypersensitivity reactions. Prostaglandins on the other hand are not causative agents of inflammation, but rather synergise with other inflammatory mediators such as histamine and bradykinin in the production of oedema and pain.
The causes of all inflammatory diseases are unknown and there are no known cures. The aetiology of each condition is often genetically-related, and is usually precipitated by environmental factors. In all inflammatory diseases there is an infiltration of inflammatory cells into the affected areas which leads to a release of mediators of the inflammatory process and concomitant damage to surrounding tissue.
Treatment of inflammatory diseases is normally based on the use of steroidal and non-steroidal anti-inflammatory drugs (NSAIDs). Steroidal drugs include the corticosteroids, for example, cortisol, prednisone, prednisolone, etc. The NSAIDs include the salicylates (e.g. aspirin), pyrazolon derivatives (e.g. phenylbutazone), para-aminophenol derivatives (e.g. phenacetin and acetaminophen), fenamates (e.g. mefenamic acid and flufenamic acid), propionic acid derivatives (e.g. ibuprofen, naproxen, fenoprofen, flurbiprofen and ketoprofen), indomethacin and tolmetin. Both classes of drugs act on arachidonic acid metabolism by inhibiting reactions in the pathways leading to the formation of prostaglandins and leukotrienes. All of the aforementioned drugs have attendant undesirable side-effects with prolonged use and in recent times some NSAIDs have been contra-indicated in certain inflammatory diseases (Rampton, D. S. and Hawkey, C. J. Gut (1984) 25, 1399).
NSAIDs have been reported to inhibit both the cyclooxygenase pathway and the lipoxygenase pathway. In particular, they appear to inhibit formation of 11- and 15-hydroxyeicosatetraenoic acid (HETE). Many cyclooxygenase and lipoxygenase pathway inhibitors are currently being investigated with a view to their being used in therapy.
Benoxaprofen, an NSAID which specifically inhibits 5-lipoxygenase, in addition to cyclooxygenase, was found to markedly improve the inflammatory skin disease psoriasis. However, benoxaprofen was found to produce adverse side effects and its use in such treatment was discontinued. The search is on-going for effective and potent anti-leukotriene agents for use against inflammatory disease by inhibition of the production of the highly potent products of the 5-, 11- and 15-lipoxygenase systems.
Taurine (2-aminoethanesulphonic acid) is found in blood plasma, urine, breast milk, saliva, cerebrospinal fluid, sweat, platelets, leukocytes, muscle, brain, skin and liver. Free taurine is found in millimolar concentrations, especially in tissues that are excitable, rich in membranes and generate reactive oxidants. The function of taurine is not known but because it is abundant where reduced oxygen molecules are generated, and where other toxic substances such as bile salts, retinoids and xenobiotics are found, it is believed that its function is related to attenuation of toxic compounds. Three metabolites of taurine have now been identified viz isethionic acid (2-hydroxyethanesulphonic acid, taurocyamine (guanidotaurine) and taurocholic acid.
Taurine has been tested as an adjunct treatment of hypercholesterolemia and in cardiovascular disorders. Taurine at 1 g per day for seven days reduced or prevented alcohol-withdrawal symptoms (Ikeda, H. Lancet (1977), 2, 509).
French Patent Publication FR-A-7241 describes pharmaceutical compositions for the treatment of arterial disease, comprising taurine and derivatives thereof.
Pharmaceutical compositions for the treatment of psoriasis and comprising at least one zwitterionic aminosulphonic acid (ZASA) compound having a pKa value at 20.degree. C. in the range 6.0-8.3 are the subject of U.S. Pat. No. 4,544,656, hereby incorporated by reference. The zwitterionic compounds include inter alia N-2-hydroxyethylpiperazine-N'-ethanesulphonic acid (HEPES). In U.S. Pat. No. 4,544,656 the anti-psoriatic effect of the ZASAs is attributed to the suppression of neutrophils. This has now been shown to be incorrect as hereinafter described. A variety of drug types are conventionally employed in the treatment of psoriasis due to the different aspects of the disease. Such drugs include anti-inflammatory drugs, anti-proliferative or cytostatic drugs and in severe cases cytotoxic drugs such as methotrexate.
U.S. Pat. No. 4,753,942, hereby incorporated by reference describes the use of the ZASAs specified in U.S. Pat. No. 4,544,656, for the topical treatment of arthritis and/or rheumatism in human patients. As demonstrated hereinafter in Example 7 skin penetration due to percutaneous absorption was not observed following topical administration of HEPES. To alleviate the symptoms of arthritis and rheumatism it would be necessary for the ZASAs to be absorbed percutaneously.